Biodegradable poly(ester-urethane-amide)s based on poly(ε- caprolactone) and diamide-diol chain extenders with crystalline hard segments. Synthesis and characterization

Article abstract of DOI:10.1021/ma300990s

Twenty seven poly(ester-urethane-amide)s (PEUAs) were synthesized from the reaction of α,ω-telechelic poly(ε-caprolactone) diols, 1,6-hexamethylene diisocyanate, and three different diamide-diol chain extenders derived from ε-caprolactone and three alipha

Full text of DOI:10.1021/ma300990s

Article
pubs.acs.org/Macromolecules
Biodegradable Poly(ester−urethane−amide)s Based on Poly(ε-
caprolactone) and Diamide−Diol Chain Extenders with Crystalline
Hard Segments. Synthesis and Characterization
́
Jose E. Baez, Daniel Ramírez, Juan L. Valentín, and Angel Marcos-Fernandez*
́
́
́
Instituto de Ciencia y Tecnología de Polímeros (CSIC), C/Juan de la Cierva 3, 28006 Madrid, Spain
S
* Supporting Information
ABSTRACT: Twenty seven poly(ester−urethane−amide)s (PEUAs) were synthesized
from the reaction of α,ω-telechelic poly(ε-caprolactone) diols, 1,6-hexamethylene
diisocyanate, and three different diamide−diol chain extenders derived from ε-caprolactone
and three aliphatic diamines with increasing length (n = 2, 4, and 6). The hard segment
(HS) was designed to be crystalline and to introduce amide groups, more susceptible to
hydrolysis than urethane or urea groups. Crystallization of the HS was achieved even at
very low HS content, leading to a phase-separated material. Furthermore, HS crystallinity
recovered from the material homogeneous melt on cooling. Thermal degradation was well
above HS melting point, allowing for melt processing of these materials. HS melting point
was affected by HS content, poly(ε-caprolactone) diol length, and chain extender length.
The length scale of the phase-separated morphology lied in between 11 and 13 nm up to
∼60% HS content and decreased at higher HS content values. HS content was the main
parameter affecting the mechanical properties. The prepared PEUAs degraded hydrolyti-
cally at very long times by surface erosion.
chain of PCL impart a hydrophobic character to the polymer,
INTRODUCTION
■
leading to long degradation times in aqueous media.8,9 α,ω-
Telechelic PCL diols (HO-PCL-OH) have been reported by
many authors as precursors in the synthesis of PUs.10−14
The aromatic diisocyanates generally used in the industrial
preparation of PUs degrade to toxic and even carcinogenic
compounds, and therefore other alternatives have been used for
biomedical applications such as L-lysine diisocyanate
(LDI),7,12−17 1,6-diisocyanatohexane (HDI),7,11,17,18 and 1,4-
diisocyanatobutane (BDI),19 which degrade to nontoxic or low
toxic diamines.
Polyurethanes (PUs) are a versatile family of polymers that
have many industrial applications due to the possibility of
tailoring their properties through their chemistry. Usually, PUs
are built from the reaction of a macroglycol, a polyisocyanate,
and a chain extender or cross-linker. When the final
macromolecule is linear, the starting reagents are a difunctional
polyol, a diisocyanate, and a difunctional chain extender, and
the resulting material is a multiblock segmented PU. The polyol
constitutes the so-called soft segments (SS), whereas the
reaction of the diisocyanate and the chain extender constitutes
the so-called hard segments (HS), and depending on the
thermodynamical incompatibility of the segments, they can
segregate in separated phases.1
PUs have been widely used in the biomedical area, mainly as
biostable materials.2 However, there is a continuous interest
since the 1990s in the development of biodegradable PUs for
controlled release of drugs and tissue engineering applica-
tions.3−7 Several reactants commonly used in the preparation of
polyurethanes such as for example 4,4′-diisocyanatodiphenyl-
methane (MDI) or 3,3′-dichloro-4,4′-diaminediphenylmethane
(MOCA or MBOCA) degrade to toxic products and therefore
have to be excluded from the synthesis of biodegradable PUs. It
is therefore necessary to make a careful choice of the reactants
in order to obtain polymers with non toxic degradation
products.
Several diols and diamines have been described as chain
extenders in the synthesis of biodegradable PUs: 1,4-
butanediol,10,14,16,18 amino acid derivatives,7,17 ester diols,7,17
diurethane diols,21 and diurea diols22 are some examples. When
reacted with the diisocyanate, the resulting urethane or urea
groups are very slowly degraded, and the introduction of more
labile functionalities such as an ester group7,17 facilitates the
degradation of the formed hard segment.
We have previously prepared segmented nontoxic biode-
gradable PUs where the hard segment was a slowly degrading
polyurea composed of amino acids.13 Because of the asymmetry
of the reactants, the hard segment did not form a separated
phase. Consequently, the mechanical properties of the
synthesized PUs were mainly dependent on the crystallinity
of the PCL. As a step forward, we intend the synthesis of new
Several possible reactants can be used as nontoxic polyols,
among them the poly(ε-caprolactone) (PCL) [−CO-
(CH2)5O−]n, which is an aliphatic polyester with biodegradable
and biocompatible properties. The methylenes in the main
Received: May 16, 2012
Revised: July 13, 2012
© XXXX American Chemical Society
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filtered and washed with acetone and chloroform. The resultant white
solid was then dried under vacuum.
nontoxic biodegradable PUs with a crystallizable hard segment.
This hard segment will separate in a phase and will strongly
influence the mechanical properties of the final PUs. In
addition, the introduction of more degradable sites in the
chemical structure of the hard segment will increase its
susceptibility to degradation with respect to the usual hard
segments with solely urethane and/or urea groups.
Some diamide−diol molecules [HO−R1−CONH−R2−
NHCO−R1−OH (where R1 and R2 are alkyl groups)] have
been used in the synthesis of poly(ester−amide)s23−25 and
poly(amide−urethane)s,26 and they have also been proposed as
chain extenders in segmented PUs.27 In the case of the
poly(amide−urethane)s, the final polymer was intended to be
used as film or in textiles with resistance to light and solvents.
In the case of the segmented PUs, the chain extenders were
derived from γ-butyrolactone or ε-caprolactone and ethanol-
amine or short aliphatic diamines, and the PUs were formulated
for castable preparations with MDI-based prepolymers.
N,N′-Hexamethylenebis(6-hydroxycaproamide) [HO-
(CH2)5CONHCH2CH2CH2]2 (HDA-2CL). The product HDA-2CL
(theoretical molecular weight = 344.3 g/mol) is a white powder.
Yield: 66%. IR (cm−1): 3306 (ν, N−H), 3054 (νs‑trans, N−H), 2935
(νas, CH2), 2860 (νs, CH2), 1630 (ν, CO), 1532 (δ, N−H), 1050
1
(ν, C−OH), 728 (ρ, CH2), 685 (ω, N−H). H NMR data for HDA-
2CL (400 MHz, DMSO-d6, ppm) (Figure 1): 7.72 (t, 1H, [NH]), 4.35
In the work presented here, we have prepared three
diamide−diol chain extenders (DCE) based on ε-caprolactone
and ethane-, butane-, and hexanediamine. These chain
extenders were reacted with three different aliphatic diisocya-
natesLDI, HDI and BDIto obtain nine model polyur-
ethane hard segments, and their crystallization ability was
evaluated. It must be noted that two of these models have been
already described in ref 26. One diisocyanate, HDI, was chosen
to synthesize 27 new poly(ester−urethane−amide)s (PEUAs)
based on PCL diol of three different molecular weights and
with different molar ratios of the reactants (or different hard
segment contents). None of the chain extenders used in this
work was used in ref 27, and therefore they have not been
previously described as components of segmented PUs. The
PEUAs chemical structure, physical properties, and hydrolytic
degradation were characterized. The results were related to the
length of the PCL, the length of the chain extender, and the
hard segment content on the PEUA.
Figure 1. 1H NMR (400 MHz) spectrum for HDA-2CL diamide−diol
chain extender in DMSO-d6. Oligomeric species of PCL are indicated
by an asterisk.
(s, 1H, [OH]), 3.35 (t, 2H, [CH2OH]), 2.99 (q, 2H, [HN−CH2]),
2.02 (t, 2H, [CH2CO]), 1.46 (q, 2H, [CH2CH2OH]), 1.37 (q, 2H,
[CH2CH2CO]), 1.37 (t, 2H, [HN−CH2−CH2]), 1.22 (q, 2H,
[CH2(CH2)2CO]), 1.22 (t, 2H, [HN−(CH2)2−CH2]). 13C NMR
(100 MHz, DMSO-d6, ppm): 171.9 (CO), 60.6 (CH2OH), 38.3
(CH2 NH), 35.5 (CH2 CO), 32.3 (CH2 CH2 OH), 29.1
(CH2(CH2)2NH), 26.1 (CH2CH2NH), 25.3 (CH2(CH2)2CO), 25.2
(CH2CH2CO). Tm (DSC) = 134 °C.
EXPERIMENTAL SECTION
N , N ′ - B u t y l e n e b i s ( 6 - h y d r o x y c a p r o a m i d e ) [ H O -
(CH2)5CONHCH2CH2]2 (BDA-2CL). The product BDA-2CL (theoretical
molecular weight = 316.2 g/mol) is a white powder. Yield: 55%. IR
(cm−1): 3302 (ν, N−H), 3058 (νs‑trans, N−H), 2942 (νas, CH2), 2866
(νs, CH2), 1630 (ν, CO), 1535 (δ, N−H), 1050 (ν, C−OH), 740
■
Materials. ε-Caprolactone (CL), tin(II) 2-ethylhexanoate Sn-
(Oct)2, 1,6-diisocyanatohexane (HDI), 1,4-butane diisocyanate
(BDI), 1,4-butylenediamine (BDA), and 1,6-hexamethylenediamine
(HDA) were purchased from Aldrich Chemical Co. and used as
received. L-Lysine diisocyanate (LDI, diisocyanate of the L-lysine
methyl ester or methyl 2,6-diisocyanatohexanoate) was kindly donated
by Kyowa Hakko Kogyo Co., Ltd., Japan, and used as received. α,ω-
Telechelic poly(ε-caprolactone) diols (HOPCLOH) [Mn(NMR) =
539, 1243, and 1923], purchased from Aldrich, were dried at 70 °C
and under vacuum for at least 5 h, and stored at ambient temperature
in a desiccator at vacuum until used. 1,2-Ethylenediamine (EDA),
purchased from Aldrich, was blended with potassium hydroxide and
distilled before use. N,N-Dimethylacetamide, purchased from Scharlau,
was vacuum-distilled from isocyanates (commercial polymeric MDI)
in order to eliminate residual water and amines that would unbalance
the stoichiometry on the synthesis of the polymers. Distillation
temperature was kept below 60 °C to avoid solvent decomposition,
and the distilled solvent was stored in an amber flask blanketed with
nitrogen for not more than a week before use.
1
(ρ, CH2), 689 (ω, N−H). H NMR data for BDA-2CL (400 MHz,
DMSO-d6, ppm): 7.73 (t, 1H, [NH]), 4.34 (s, 1H, [OH]), 3.36 (t, 2H,
[CH2OH]), 2.99 (t, 2H, [HN−CH2]), 2.02 (t, 2H, [CH2CO]), 1.46
(q, 2H, [CH2CH2OH]), 1.35 (q, 2H, [CH2CH2CO]), 1.35 (t, 2H,
[HN−CH2−CH2]), 1.23 (q, 2H, [CH2(CH2)2CO]). 13C NMR (100
MHz, DMSO-d6, ppm): 172.0 (CO), 60.6 (CH2OH), 38.1
(CH2NH), 35.5 (CH2CO), 32.3 (CH2CH2OH), 26.7 (CH2CH2NH),
25.3 (CH2(CH2)2CO), 25.2 (CH2CH2CO). Tm (DSC) = 140 °C.
N,N′-Ethylenebis(6-hydroxycaproamide) [HO(CH2)5CONHCH2]2
(EDA-2CL). The product EDA-2CL (theoretical molecular weight =
288.2 g/mol) is a white powder. Yield: 36%. IR (cm−1): 3297 (ν, N−
H), 3083 (νs‑trans, N−H), 2939 (νas, CH2), 2858 (νs, CH2), 1637 (ν,
CO), 1556 (δ, N−H), 1047 (ν, C−OH), 768 (ρ, CH2), 718 (ω,
1
N−H). H NMR data for EDA-2CL (400 MHz, DMSO-d6, ppm):
7.79 (t, 1H, [NH]), 4.34 (s, 1H, [OH]), 3.36 (t, 2H, [CH2OH]), 3.06
(t, 4H, [HN−(CH2)2−NH]), 2.02 (t, 2H, [CH2CO]), 1.46 (q, 2H,
[CH2CH2OH]), 1.38 (q, 2H, [CH2CH2CO]), 1.23 (q, 2H,
[CH2(CH2)2CO]). 13C NMR (100 MHz, DMSO-d6, ppm): 172.5
(CO), 60.7 (CH2OH), 38.4 (CH2NH), 35.6 (CH2CO), 32.3
(CH2CH2OH), 25.3 (CH2(CH2)2CO), 25.2 (CH2CH2CO). Tm
(DSC) = 156 °C.
Synthesis of Diamide−Diol Chain Extenders. Reaction was
carried out in a 100 mL round-bottom flask previously dried. In a
reaction example, 1,6-hexamethylenediamine (HDA) (3 g, 25.8 mmol)
and ε-caprolactone (CL) (44.1 g, 387 mmol) were charged and heated
in a reflux system by stirring them in an oil bath a 70 °C for 2 h (CL/
HDA molar ratio ≈15). After cooling the reaction mixture at room
temperature a white precipitate was obtained. The precipitate was
Synthesis of Poly(urethane−amide) Hard Segment Models.
Reaction was carried out in a 50 mL round-bottom flask previously
B
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dried. In a reaction example, HDA-2CL diamide−diol chain extender
(0.500 g, 1.4 mmol), 1,6-diisocyanatohexane (HDI) (0.235 g, 1.4
mmol), and 5.3 mL of dry N,N-dimethylacetamide (DMA) (20% w/v)
as solvent were charged and heated in a reflux system with stirring at
80 °C. After dissolution of the monomers, tin(II) 2-ethylhexanoate
(12 mg, one drop) was added, and the reaction mixture was stirred for
further 12 h at 80 °C. The crude reaction was poured over an excess of
cool water, and a white solid was precipitated, filtered, and dried under
vacuum. Yield was quantitative.
Poly(urethane−amide) (PUA1) Derived from EDA-2CL and HDI.
The product PUA1 is a white powder. IR (cm−1): 3304 (ν, N−H),
3075 (νs‑trans, N−H), 2938 (νas, CH2), 2861 (νs, CH2), 1680 (ν, C
O, urethane), 1638 (ν, CO, amide), 1534 (δ, N−H), 1262 (δ, C−
N−H), 1052 (ν, C−O, urethane), 729 (ρ, CH2). Tm (DSC) = 205 °C.
Poly(urethane−amide) (PUA2) Derived from BDA-2CL and HDI.
The product PUA2 is a light yellow powder. IR (cm−1): 3298 (ν, N−
H), 3061 (νs‑trans, N−H), 2934 (νas, CH2), 2858 (νs, CH2), 1677 (ν,
CO, urethane), 1632 (ν, CO, amide), 1534 (δ, N−H), 1260 (δ,
C−N−H), 1050 (ν, C−O, urethane), 733 (ρ, CH2). Tm (DSC) = 188
°C.
Poly(urethane−amide) (PUA3) Derived from HDA-2CL and HDI.
The product PUA3 is a light yellow powder. IR (cm−1): 3305 (ν, N−
H), 3061 (νs‑trans, N−H), 2932 (νas, CH2), 2856 (νs, CH2), 1675 (ν,
CO, urethane), 1616 (ν, CO, amide), 1572 (δ, N−H), 1536 (δ,
N−H), 1262 (δ, C−N−H), 1050 (ν, C−O, urethane), 732 (ρ, CH2).
Tm (DSC) = 168 °C.
Poly(urethane−amide) (PUA4) Derived from EDA-2CL and BDI.
The product PUA4 is a white powder. IR (cm−1): 3305 (ν, N−H),
2941 (νas, CH2), 1681 (ν, CO, urethane), 1639 (ν, CO, amide),
1537 (δ, N−H), 1281 (δ, C−N−H), 1048 (ν, C−O, urethane). Tm
(DSC) = 213 °C.
Poly(urethane−amide) (PUA5) Derived from BDA-2CL and BDI.
The product PUA5 is a white powder. IR (cm−1): 3302 (ν, N−H),
2943 (νas, CH2), 1681 (ν, CO, urethane), 1636 (ν, CO, amide),
1534 (δ, N−H), 1281 (δ, C−N−H), 1049 (ν, C−O, urethane). Tm
(DSC) = 211 °C.
Poly(urethane−amide) (PUA6) Derived from HDA-2CL and BDI.
The product PUA6 is a white powder. IR (cm−1): 3302 (ν, N−H),
2934 (νas, CH2), 1682 (ν, CO, urethane), 1632 (ν, CO, amide),
1532 (δ, N−H), 1044 (ν, C−O, urethane). Tm (DSC) = 192 °C.
Poly(urethane−amide) (PUA7) Derived from EDA-2CL and LDI.
The product PUA7 is a light yellow powder. IR (cm−1): 3296 (ν, N−
H), 2941 (νas, CH2), 1688 (ν, CO, urethane), 1640 (ν, CO,
amide), 1538 (δ, N−H), 1048 (ν, C−O, urethane). Tm (DSC) = 125
°C.
urethane−amide) (PEUA) film was obtained by casting in a leveled
glass within a fume cupboard. The cast solution was covered with a
conical funnel to protect it from dust and to avoid an excessively fast
solvent evaporation and allowed to stand at 80 °C for 12−15 h. After
this time, the PEUA film was released and dried for further 12−24 h in
vacuum.
Three different molar ratios HOPCLOH:HDI:DCE (1:1.5:0.5,
1:2.5:1.5, and 1:3.5:2.5) were used in this work for each one of the
chain extenders (EDA-2CL, BDA-2CL, and HDA-2CL) and macro-
diols HO-PCL-OH (Mn(NMR) = 539, 1243, and 1923). In Table S1
(Supporting Information) all the synthesized polymers are detailed.
The poly(ester−urethane−amide)s (PEUA)s were named PU-XY-ZZ
following this code: PU refers to poly(ester−urethane−amide); X
refers to the Mn(RMN) of poly(ε-caprolactone) diol (1 = 1923, 2 =
1243, 3 = 539); Y refers to the chain extender type (E = EDA-2CL, B
= BDA-2CL, H = HDA-2CL), and ZZ refers to the hard segment
content of the polymer (wt %), defined as [(weight HDI + weight
chain extender)/total polymer weight]. Finally, by this method 27
different PEUAs were synthesized.
Spectrometric data for PU-2B-42: IR (cm−1): 3312 (ν, N−H,
amide), 2935 (νas, CH2), 2862 (νs, CH2), 1726 (ν, CO, ester), 1660
(ν, CO, urethane), 1631 (ν, CO, amide), 1536 (δ, N−H, amide),
1
1237 (δ, C−N−H), 1161 (δ, O−CO, ester), 732 (ρ, CH2). H
NMR data (400 MHz, DMSO-d6, ppm): 7.72 (t, 1H, [NH], amide),
7.15 (1H, [NH], urethane), 7.00 (1H, [NH], urethane), 5.70 (1H,
[NH], urethane), 4.34 (t, 2H, [CH2OH]), 4.10 (2H, a, [O−CH2]),
3.97 (t, 2H, g, [CH2−OCO]), 3.88 (t, 2H, D, [CH2−OCONH]), 3.59
(2H, b, [OCH2CH2OCO]), 3.36 (t, 2H, [CH2OH]), 2.99 (t, 2H, J,
[CH2NHCO]), 2.92 (2H, A, [CH2NHCOO]), 2.26 (t, 2H, c,
[CH2COO]), 2.02 (t, 2H, I, [CH2CONH]), 1.52 (2H, d,E, f,
[CH2]), 1.28 (2H, e,B,C,G,K, [CH2]), 1.22 (2H, F,L, [CH2]). 13C
NMR (100 MHz,DMSO-d6, ppm): 172.7 (CO, ester), 171.9 (C
O, amide), 156.2 (CO, urethane).
1
Methods. Solution H and 13C NMR spectra were recorded at
room temperature on a Varian Inova 400 (400 MHz 1H and 100 MHz
13C). DMSO-d6 was used as solvent. Spectra were referenced to the
residual solvent [δ (ppm) 2.50 (1H) and 39.51 (13C)].
DSC was performed in a Mettler Toledo DSC822e instrument. Two
scans (25−210 and −90−210 °C) were performed by using a heating
rate of 10 °C/min and cooling (210 to −90 °C, 10 °C/min) the
instrument between runs under nitrogen purge. The melting points
(Tm) are given as the maximum of the endothermic transition, and the
data reported are taken from the second scan unless otherwise stated
in the text. The degree of crystallinity (xi) for the PCL soft segment
was calculated from the endothermic peak area ΔHi by xi = ΔHi/ΔHi0,
where ΔHi0 is the heat of fusion for perfect PCL crystals (135.3 J/g).28
Thermogravimetric analysis (TGA) was carried out in a TA Q500
instrument. Samples weighing between 10 and 20 mg were scanned in
Hi-Resolution mode with an initial heating rate of 10 °C/min under a
flux of nitrogen.
Poly(urethane−amide) (PUA8) Derived from BDA-2CL and LDI.
The product PUA8 is an off-white powder. IR (cm−1): 3295 (ν, N−
H), 2941 (νas, CH2), 1687 (ν, CO, urethane), 1633 (ν, CO,
amide), 1537 (δ, N−H), 1048 (ν, C−O, urethane). Tm (DSC) = 115
°C.
Poly(urethane−amide) (PUA9) Derived from HDA-2CL and LDI.
The product PUA9 is a white powder. IR (cm−1): 3297 (ν, N−H),
2934 (νas, CH2), 1689 (ν, CO, urethane), 1633 (ν, CO, amide),
1536 (δ, N−H), 1049 (ν, C−O, urethane). Tm (DSC) = 97 °C.
Synthesis of a Poly(ester−urethane−amide)s (PEUA). A
typical reaction was carried out in a 50 mL round-bottom flask
previously dried by using the prepolymer method. As an example, the
reaction procedure for polymer PU-2H-26 will be described.
First step [prepolymer]: α,ω-telechelic poly(ε-caprolactone) diol
(HOPCLOH, Mn(NMR) = 1243) (1.545 g, 1.243 mmol), 1,6-
diisocyanatohexane (HDI) (0.313 g, 1.864 mmol), tin(II) 2-ethyl-
hexanoate (24 mg, two drops), and 3.7 mL of dry N,N-
dimethylacetamide (DMA) (50% w/v) as solvent were charged and
heated in a reflux system with stirring at 80 °C for 3 h. Second step
[chain extension]: after prepolymerization, diamide−diol chain
extender (DCE) N,N′-hexamethylenebis(6-hydroxycaproamide)
(HDA-2CL) (731 mg, 2.0595 mmol) and 3.2 mL of DMA (30% w/
v final concentration) were added, and the reaction mixture was stirred
for a further 3 h at 80 °C and then left overnight at room temperature
(HOPCLOH:HDI:HDA-2CL molar ratio = 1:1.5:0.5). A poly(ester−
SAXS measurements were taken at beamline BM16 at the European
Synchrotron Radiation Facility (Grenoble, France). Samples were
placed in between aluminum foils within a Linkam hot stage and
heated at 10 °C/min while the SAXS spectra were recorded.
Calibration of temperature gave a difference of ∼7 °C between the
temperature reading at the hot stage display and the real temperature
at the sample.
FT-IR spectra of the polymer films were obtained with an
attenuated total reflectance spectroscopy (ATR) accessory in a
Perkin-Elmer Spectrum One FT-IR spectrometer.
Tensile properties were measured in a MTS Synergie 200 testing
machine equipped with a 100 N load cell. Type 3 dumbbell test pieces
(according to ISO 37) were cut from the films. A crosshead speed of
200 mm/min was used. Strain was measured from crosshead
separation and referred to 12 mm initial length. Five samples were
evaluated for each PEUA.
GPC measurements were determined using a PerkinElmer gel
permeation chromatograph (Series 200 LC pump) equipped with a
refractive index detector (IR 200a). A set of ResiPore columns
(Polymer Laboratories) conditioned at 70 °C were used to elute
C
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Scheme 1. Synthesis of Diamide−Diol (DCE) Chain Extenders
samples at the flow rate of 0.3 mL/min of HPLC-grade N,N-
dimethylformamide (DMF) with LiBr (0.1 wt %). Poly(methyl
methacrylate) standards (Polymer Laboratories) were used for
calibration.
In vitro degradation of the polymers was evaluated by measuring the
weight change of the hydrated polymer film in a phosphate buffer
solution at 37 °C without solution renovation. A certain amount of
film was put into a vial of 20 mL capacity, filled with buffer solution,
closed, and deposited in an incubator at 37 °C. At selected time
intervals the films were extracted, blotted with tissue paper,
immediately weighed, and returned to the vial. The water uptake
PCL oligomers [CH2O, δ 3.97 and CH2CO, δ 2.26] (∼3%)
was detected in all samples, marked by an asterisk in Figure 1.
This result demonstrates that propagation was almost
completely avoided with this synthetic procedure. The FT-IR
spectrum confirmed the structure of the reaction products, and
two bands related to the vibrations of amide group at 1630 (ν,
CO, amide I) and 1532 cm−1 (δ, N−H amide II) were
detected.
Diamide−diols were analyzed by DSC (Table 1, entries 1−
3), and the melting temperature (Tm) was found to be inversely
percentage was calculated as follows: weight change (%) = [(Wm
−
W0)/W0] × 100 where Wm is the weight of hydrated specimen and W0
is the initial weight of the specimen. Polymers were tested in duplicate.
Scanning electron microscopy (SEM) photographs were taken in a
Philips XL30 environmental scanning electron microscope at high
vacuum operated at 25 kV.
Table 1. Thermal Properties of Diamide−Diol Chain
Extenders (DCE) and Model Hard Segment Poly(urethane−
amide)s (PUA)s Obtained by DSC
run 1
run 2
Tm
(°C)
ΔHm
Tm
(°C)
ΔHm
no.
1
sample
chain
composition
EDA-2CL
(J/g)
167.0
(J/g)
RESULTS AND DISCUSSION
■
156
140
134
205
188
168
213
211
192
125
115
97
Synthesis of Diamide−Diol Chain Extenders (DCE). In
previous works, we have prepared biodegradable nontoxic
polyurethanes based on an amino acid disocyanate, LDI, and
amino acid chain extenders.13 Because of the asymmetry of
these reactants, the hard segments of the final segmented
polyurethanes were amorphous and mixed with soft segments.
As a result, the main contribution to the mechanical properties
of the resulting materials came from the crystallization of the
soft segments. In this work, we try to prepare new segmented
polyurethanes with crystalline hard segments that will promote
a phase-separated morphology. This morphology will influence
all the physical properties including the mechanical.
extender
chain
extender
chain
extender
PUA1
2
3
4
5
6
7
8
9
BDA-2CL
HDA-2CL
156.4
154.4
91.1
EDA-2CL +
HDI
192
175
136
207
208
178
73.6
66.8
6.1
PUA2
PUA3
PUA4
PUA5
PUA6
BDA-2CL +
HDI
88.7
HDA-2CL +
HDI
84.1
EDA-2CL +
BDI
104.0
101.8
92.9
78.8
79.5
53.7
4.2
BDA-2CL +
BDI
Three diamide−diol chain extenders [HO(CH2)5CONH-
(CH2)nNHCO(CH2)5OH, where n = 2 (EDA-2CL), 4 (BDA-
2CL), and 6 (HDA-2CL)] derived from ε-caprolactone (CL)
and three different aliphatic diamines [HN2−(CH2)n−NH2, n =
2, 4, 6] were synthesized by ring-opening of ε-CL (Scheme 1).
The starting diamines were chosen because of their relatively
low toxicity, which makes them good candidates for the
preparation of biodegradable materials, and for their symmetric
structure, that will favor the crystallization of the corresponding
synthesized chain extenders. In addition, the introduction of
amide groups in the chain extender structure is expected to
facilitate the hydrolysis of the hard segments by acidic or basic
conditions and by the assistance of enzymes respect to hard
segments bearing only urethane functional groups. The
synthesis of the chain extenders was carried out in a great
excess of ε-CL at moderate temperature without presence of
catalyst in order to avoid the propagation reaction of the ε-CL.
Chemical structures were corroborated by 1H NMR and FT-IR.
For the case of HDA-2CL chain extender, 1H NMR spectrum is
shown in Figure 1. Signals corresponding to amide group
[CONH, f, δ 7.72], methylenes close to hydroxyl group
[CH2OH, a, δ 3.35], and methylenes close to amide group
[CH2NHCO, h, δ 2.99] were observed. A minimum amount of
HDA-2CL +
BDI
a
10 PUA7
11 PUA8
12 PUA9
EDA-2CL +
LDI
44.2
113
a
BDA-2CL +
LDI
41.0
110
3.0
a
HDA-2CL +
LDI
53.2
−
−
a
For LDI-based poly(urethane−amide)s, a Tg is found in the second
run with a value of 28, 25, and 22 °C for PUA7, PUA8, and PUA9,
respectively.
proportional to the number of methylenes between diamide
groups. This result was expected because the density of amide
groups increases when the chain extender length decreases. The
measured melting points for diamide−diol were generally
higher than values reported in the literature, but a higher purity
of our monomers cannot be concluded because the measure-
ment method was not detailed29,30 or was different from
ours.24,27 Thus, Tm = 156−157 °C27 (similar to the value
measured by us), 143 °C,29 126 °C,24 and 116−117 °C30 have
been reported for EDA-2CL; 140 °C30 (140 °C measured by
D
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Table 2. Composition, Solubility, and Number-Average Molecular Weight (Mn) for the Synthesized Poly(ester−urethane−
amide)s (PEUA)s
Mn(NMR)
HOPCLOH
diamide−diol chain extender molar ratio HOPCLOH:
hard segment
solubility DMF
a
b
c
d
f
e
e
PEUA
(DCE)
HDI:DCE
(wt %)
(LiBr 0.1%)
Mn(GPC) Mw/Mn
g
PU-1E-17
PU-1E-31
PU-1E-41
PU-2E-24
PU-2E-41
PU-2E-52
PU-3E-43
PU-3E-62
PU-3E-71
PU-1B-18
PU-1B-32
PU-1B-42
PU-2B-25
PU-2B-42
PU-2B-53
PU-3B-43
PU-3B-63
PU-3B-72
PU-1H-18
PU-1H-33
PU-1H-43
PU-2H-26
PU-2H-43
PU-2H-54
PU-3H-44
PU-3H-64
PU-3H-73
1923
1923
1923
1243
1243
1243
539
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
1:1.5:0.5
1:2.5:1.5
1:3.5:2.5
17
31
41
24
41
52
43
62
71
18
32
42
25
42
53
43
63
72
18
33
43
26
43
54
44
64
73
+
34 100
22 900
1.67
1.52
h
+
h
−
g
+
49 600
20 400
2.11
1.56
h
+
h
−
−
−
−
h
h
539
h
539
g
1923
1923
1923
1243
1243
1243
539
+
26 800
20 800
1.67
1.52
h
+
h
−
g
+
27 600
15 500
1.86
1.50
h
+
h
−
h
+
18 900
1.68
h
539
−
−
h
539
g
1923
1923
1923
1243
1243
1243
539
+
32 400
20 100
1.64
1.54
h
+
h
−
h
+
44 900
14 600
1.79
1.44
h
+
h
−
h
+
32 700
1.70
h
539
−
−
h
539
a
PU-XY-ZZ where PU is poly(ester−urethane−amide), X is the Mn(RMN) of poly(ε-caprolactone) diol (1 = 1923, 2 = 1243, 3 = 539), Y is the
b
c
chain extender type (E = EDA-2CL, B = BDA-2CL, H = HDA-2CL), and ZZ is the hard segment content (wt %). Obtained by 1H NMR. EDA-
2CL = [HO(CH2)5CONHCH2]2, BDA-2CL = [HO(CH2)5CONHCH2CH2]2, and HDA-2CL = [HO(CH2)5CONHCH2CH2CH2]2. Hard
segment (%) = (weight of HDI + weight of chain extender)/total weight of monomers × 100. Determined by gel permeation chromatography
(GPC). (+) Soluble, (−) insoluble, and ( ) partially soluble. At room temperature (rt). At room temperature after heating at 190 °C.
d
e
f
g
h
us), 95 °C,29 and 88 °C24 for BDA-2CL; and 135−136
°C27(134 °C measured by us), 135 °C,29 129 °C,30 and 95 °C24
for HDA-2CL.
12) demonstrated that model hard segments were crystalline.
Melting temperatures for BDI- and HDI-based models
precipitated from solution (run 1) were high, slightly higher
for BDI based models where the density of urethane groups is
higher. Melting temperature for PUA1 was similar to the value
reported in the literature (192−204 °C), and for PUA3 it was
slightly lower to reported (178−187 °C).27 Surprisingly, LDI-
based materials were also crystalline, although with melting
temperatures much lower than for the other models. After
recrystallization (run 2), melting temperatures for BDI- and
HDI-based models decreased, with a larger decrease for HDI-
based models, although in all cases the melting temperature was
well above ambient temperature. The amount of crystallinity
was also reduced as seen in the melting enthalpy values, very
strongly for PUA3, based on HDI and HDA-2CL. This
decrease was expected because the ordering of the chains for
crystallization is more difficult in the melt than when
precipitated from solution. For LDI-based models, the material
was amorphous after cooling from the melt, and a clear Tg was
obtained at values around ambient temperature, with a slight
decrease on the value when the length of the diamine increased.
After Tg was reached, for polymers PUA7 and PUA8, a
crystallization exotherm appeared followed by a melting
endotherm with a low enthalpy value; thus, crystallization was
very strongly reduced, and for polymer PUA9, crystallinity was
completely lost.
Synthesis of Model Poly(urethane−amide)s (PUA)s
Hard Segments. In the synthesis of poly(ester−urethane−
amide)s PEUAs, the hard segment is built up by the reaction of
the diamide−diol chain extender (DCE) and a diisocyanate.
Consequently, as part of a sequential study, poly(urethane−
amide)s (PUA)s hard segment models were synthesized by
reacting, in equimolar proportions, the diamide−diols species
previously obtained and several diisocyanates, namely HDI,
BDI, and LDI. These diisocyanates were chosen because their
resulting hydrolysis products, L-lysine, 1,4-butanediamine, and
1,6-hexanediamine, are nontoxic or have a relatively low
toxicity, especially if compared to the commonly used aromatic
diisocyanates, most of them producing carcinogenic diamines
after hydrolysis. LDI has an asymmetric structure, and the
crystallinity of the derived poly(urethane−amide)s was
expected to be low. On the other hand, BDI and HDI are
symmetrical, and highly crystalline poly(urethane−amide)s
were expected.
The reaction proceeded with quantitative yields at 80 °C for
12 h. FT-IR spectra for all PUAs samples presented
characteristic stretching vibrations for carbonyl group (C
O) of urethane and amide at 1675−1680 and 1616−1638
cm−1, respectively. DSC results shown in Table 1 (entries 4−
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There exists an evident relationship between melting
temperature of the model polymers and the length of the
chain extender. Melting temperature decreased when chain
extender length increased. This is due to the decrease in the
density of polar groups in the polymer. For BDI- and HDI-
based models, there is an increase in Tm value respect to the
diamide−diol precursors (entries1−3). This increase can be
explained by the stronger intermolecular hydrogen bonding of
the urethane groups respect to the amide groups. However, for
LDI-based models, the asymmetry of the LDI diisocyanate
probably results in low order crystals that melt at even lower
temperatures than the corresponding diamide−diol precursors.
For the synthesis of the segmented poly(ester−urethane−
amide)s, LDI was rejected because of the low crystallinity found
in the models. It was expected that crystallinity was even lower
in the segmented poly(ester−urethane−amide)s, where the
length of the hard segment moiety would be reduced with
respect to the hard segment model homopolymers. In the case
of BDI and HDI diisocyanates, both produced hard segments
models with relatively high crystallinity and high melting
temperatures. They have been used in the preparation of
biodegradable polyurethanes, but for the preparation of the
segmented poly(ester−urethane−amide)s in this work, HDI
was chosen because of its much lower cost, commercial
availability in large quantities, and lower volatility. HDI derived
hard segments have and additional advantage respect to the
BDI derived hard segment models; that is, their lower melting
temperature will reduce the processing temperature if
processed from the melt, reducing the possibility of thermal
degradation.
The measured molecular weights of the polymers that were
soluble at 70 °C (Table 2) are typical for these segmented
polymers, with a relatively broad polydispersity index in
between 1.5 and 2.1 and values for molecular weight (Mn) in
between Mn = 15 000 and 50 000 g/mol.13 The only noticeable
trend is the decrease in molecular weight when the molar ratio
increases (hard segment content increases) for polymers with
the same chemical structure.
Characterization of Poly(ester−urethane−amide)s
(PEUA)s. Nuclear Magnetic Resonance (NMR). In Figure 2,
1
Figure 2. H NMR (400 MHz) spectrum for poly(ester−urethane−
amide) PU-2H-26 in DMSO-d6.
Synthesis of Poly(ester−urethane−amide)s (PEUA)s.
Three molar ratios of the reactants PCL:HDI:DCE were
chosen for the synthesis of the PEUAs: 1:1.5:0.5, 1:2.5:1.5, and
1:3.5:2.5. It is accepted that, in general, for linear polyurethanes
it is necessary a minimum molar ratio of 1:2:1 in order to
achieve a phase-separated morphology. The three molar ratios
tested in this study are below this ratio, above this ratio, and
well above this ratio, in order to check the thermodynamical
incompatibility of these new chain extenders.
1
the H NMR spectrum of poly(ester−urethane−amide) (PU-
2H-26) derived from the reaction of HOPCLOH, HDI, and
HDA-2CL (Table 2) is shown. The characteristics signals of
methylenes close to ester [−CH2−O−(CO)−, δ 3.97],
urethane [−CH2−NH−(CO)−O−, δ 2.92], and amide
[−CH2−NH−(CO)−, δ 2.99] functional groups demon-
strated that the HDA-2CL diamide−diol chain extender could
be introduced in the main chain of the PEUA. The isocyanate
group was not detected, indicating its complete reaction. The
rest of the peaks were assigned in base to references in the
area.12,13,31 Complementary, 13C NMR spectrum in Figure 3
shows the peaks for the carbonyl zone for three different
samples: (a) α,ω-telechelic poly(ε-caprolactone) diol HOP-
CLOH [−(CO)−O−, δ 172.7], (b) HDA-2CL diamide−
diol chain extender [−(CO)−NH−, δ 171.9], and (c)
poly(ester−urethane−amide) PU-2H-26. For the latter, three
different signals corresponding to ester, amide, and urethane
[−O−(CO)−NH, δ 156.2] groups were observed. This
evidence corroborated the presence of the functional groups
After casting from the reaction solution and drying, the
resulting polymeric films were very insoluble (Table S2). Only
a few polymers, with the lower PCL:HDI:DCE molar ratio,
were soluble at room temperature in polar solvents (DMSO,
DMF, or DMF with 0.1 wt % LiBr). Heating the polymers in
DMF with 0.1 wt % LiBr at 190 °C dissolved the polymers with
1:1.5:0.5 and 1:2.5:1.5 molar ratio, except for the polymer PU-
3E-43. In this particular case, a gel was formed during reaction,
probably due to cross-linking through allophanate reaction
(reaction of isocyanate with urethane groups) or even N-
acylurea reaction (reaction of isocyanate with amide groups).
For polymers with the highest molar ratio, 1:3.5:2.5, only a few
dissolved but reprecipitated on cooling. For these series, also a
gel was formed for polymers PU-3E-71 and PU-3B-72 during
the synthesis. It is therefore clear that lower solubility of the
polymers was obtained by using higher molar ratios (longer
hard segments). For the polymers with the lower molar ratio,
1:1.5:0.5, with a hard segment content in between 17 and 44 wt
%, the polymers remained soluble on cooling. For the
intermediate ratio, 1:2.5:1.5, hard segment content limited
their solubility; thus, up to 43% hard segment weight remained
soluble on cooling, whereas at 62−64% hard segment weight
the polymers reprecipitated on cooling.
1
attributed to PU-2H-26 and observed by H NMR (Figure 2).
Infrared Analysis. FT-IR spectroscopy resulted very useful
for the characterization of the carbonyl groups present in the
synthesized PEUAs. The sequential assignation of carbonyls
groups with different environments is shown in Figure 4. In the
case of α,ω-telechelic poly(ε-caprolactone) diol (HOPCLOH)
(Figure 4a) a single band of carbonyl stretching vibrations at
1722 cm−1 corresponding to ester group [−(CO)−O−] was
observed. On the other hand, HDA-2CL diamide−diol chain
extender (Figure 4b) showed the characteristic bands of amide
I from CO stretching vibration and amide II from N−H
bending with C−N stretching vibration at 1630 and 1532 cm−1,
F
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Figure 3. 13C NMR (100 MHz) spectra of the carbonyl zone: (a) α,ω-
hydroxypoly(ε-caprolactone) diol (HOPCLOH, Mn(NMR) = 1923),
(b) N,N′-hexamethylenebis(6-hydroxycaproylamide) (HDA-2CL),
and (c) poly(ester−urethane−amide) PU-2H-26.
respectively. A similar pattern was observed in the other two
EDA-2CL and BDA-2CL diamide−diol chain extenders. In
Figure 4c, a model poly(urethane−amide) (PUA3, Table 1)
derived from HDA-2CL and HDI is shown. Two pairs of bands
can be seen: (a) the first assigned to urethane group at 1675
and 1572 cm−1 due to carbonyl CO stretching vibration and
N−H bending with C−N stretching vibration, respectively, and
(b) the second pair corresponding to amide I (1616 cm−1) and
II (1536 cm−1) previously assigned for HDA-2CL. It is
interesting to note that in PUA3 the IR bands tended to
broaden, probably because of amide−urethane interactions by
hydrogen bonding. Finally, PEUA PU-2H-26 derived from
HOPCLOH, HDI, and HDA-2CL showed bands previously
attributed at ester, urethane, and amide groups (see Figure 4d).
Additionally, in PU-2H-26, other important vibrations could be
detected in the spectrum, e.g., N−H stretching, CH2 asym-
metrical stretching, and CH2 symmetrical stretching at 3312,
2935, and 2862 cm−1, respectively. Similar signals were also
found in all PEUAs samples.
Thermogravimetric Analysis (TGA). It is known that
polyurethanes are thermally unstable at high temperature. In
the thermogravimetric analysis (TGA) for all PEUAs samples,
three steps in the curve (Figure 5 and Table 3) were observed.
It has been reported that the first weight loss during thermal
degradation of segmented polyurethanes is due to the
degradation of the hard segment as a consequence of the
relatively low thermal stability of the urethane groups whereas
the second weight loss has been associated with soft segment
decomposition.32 Similar behavior has been found for
segmented poly(urethane−urea)s.13,33 In those cases, during
hard segment degradation, the parent diisocyanate and chain
extender were released, and the weight percentage of the loss
was roughly the weight percentage of diisocyanate plus chain
extender in the feed. In our PEUAs, the first weight loss, Td1 at
258−277 °C, did not correspond in weight to the hard segment
content of the polymers. In fact, the first weight loss was above
Figure 4. FT-IR spectra of the carbonyl zone: (a) α,ω telechelic
poly(ε-caprolactone) diol (HO-PCL-OH) (Mn(NMR) = 1243), (b)
amide diol (HDA-2CL) chain extender, (c) poly(urethane−amide)
derived from HDI and HDA-2CL, and (d) poly(ester−urethane−
amide) (PEUA) derived from PCL:HDI:HDA-2CL (molar ratio
1:1.5:0.5).
the soft segment content of the polymers and close to it for
PEUAs with hard segment based on HDA-2CL (see Table 3).
However, the degradation temperature of this step decreased
when the hard segment content increased, as seen in Figure 5
and Table 3. It demonstrated the lower stability of the urethane
bonds respect to the amide and ester groups present in the
PEUAs structure. This behavior is not contradictory and is due
to the structure of the chain extender. When the temperature of
degradation for urethane groups was reached, the diisocyanate
units were released, but not the chain extender diamide units,
because they are less volatile than usual chain extenders, e.g.,
G
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hard segment models, leaving a wide window for melt
processing of these polymers.
Differential Scanning Calorimetry (DSC). Both PCL and
hards segments based on diamide−diol chain extenders (DCE)
used in this work were semicrystalline. Therefore, a phase
segregation with two different crystalline phases could be
present in the PEUAs. Table 4 shows the thermal properties
from PEUAs obtained by DSC in the second heating step, and
Figure 6 displays some curves for PEUAs with different hard
segment content (17−43%) derived from EDA-CL, as an
example.
In all PEUA samples the hard segment (HS) was crystalline
with a melting temperature (Tm2) from 88 to 179 °C. It is
important to note that even at a molar ratio 1:1.5:0.5, below the
ratio 1:2:1 generally accepted to be the minimum to achieve
phase separation, these PEUAs showed phase segregation. It
indicates the strong thermodynamical incompatibility of the
hard segments derived from HDI and these diamide−diol chain
extenders. Moreover, PEUAs derived from PCL with
Mn(NMR) = 1923 (PU-1Y-ZZ) and 1243 (PU-2Y-ZZ) showed
crystallizable soft segment (SS) (Tm1 = 7−40 °C), whereas for
PEUAs synthesized from PCL with Mn(NMR) = 539 (PU-3Y-
ZZ) the soft segment always remained amorphous.
Tg values for the soft segment were in between −52 and −55
°C for PEUAs based on PCL of molecular weight 1923 and
1243 g/mol independent of the HS content and the chain
extender structure. This value was 5−8 °C higher than for PCL
homopolymer of similar molecular weight34 due to the mobility
restrictions imposed by the HS on the chain ends. These results
demonstrate that soft segments are well separated in an almost
pure phase or at least in a phase with a very limited hard
segment mixing. For PEUAs based on short PCL, 539 g/mol,
Tg values were much higher, as expected, increasing when HS
content increased due to the increase in the rigidity of the
polymer, with very high HS contents (43−73%). The difference
in Tg values for some polymers of this series (PU-3E-43, PU-
3E-71, and PU-3B-72) with the same HS content and different
chain extender structure was unexpected. These differences in
Tg are due to the cross-link produced during polymerization, as
mentioned in the discussion of the synthesis of these PEUAs.
Thus, polymer PU-3E-43 had a Tg of −35 °C, 5 °C higher than
PU-3B-43 and PU-3H-44, whereas PU-3E-71 and PU-3B-72
had a Tg of −16 and −18 °C, respectively, very high compared
to the Tg of −30 °C for PU-3H-73. In segmented poly-
(urethane−urea)s previously synthesized by us, based on lysine
diisocyanate and lysine or ornithine chain extender, where the
PCL soft segment was partially segregated and partially mixed
with the hard segments, Tg values for polymers based on PCL
of 539 g/mol were −6.9 and −10 °C, respectively.13 These
Figure 5. TGA of PEUAs derived from HDA-2CL with molar ratio
1:1.5:0.5 and different PCL diol length.
butanediol. The release of the diisocyanate was followed by the
degradation of the polycaprolactone chains, giving all together
the first weight loss in the thermogravimetric curve. This is the
reason why the weight change was higher than the
polycaprolactone content in the polymer. Following this
reasoning, the second weight change in these PEUAs, Td2,
was assigned to the degradation of the chain extender entering
the hard segment. This weight loss took place at 282−315 °C,
in the range of degradation temperatures reported by Katayama
et al. for PUA1 and PUA3 (305 °C),27 supporting the
assumption that it was related to the diamide−diol chain
extender degradation. In addition, the weight change in this
step increased with the increase in hard segment content
(Figure 5), and for the PEUAs based on HDA-2CL it
approached the diamide−diol content in the polymer (Table
3). For PEUAs based on BDA-2CL and EDA-2CL, the first
weight loss was much higher than the PCL content in the
polymer, and the second weight loss was much lower than the
diamide−diol content in the polymer. It seems that for these
polymers part of the chain extender was released with the PCL
in the first weight loss. It could be probably due to the joint
effect of higher volatility because of the shorter chain of the
extender and the higher onset of decomposition. From the data
in Table 3 it can be deduced that the onset of degradation is
slightly dependent on the chain extender length following the
trend HDA-2CL < BDA-2CL < EDA-2CL. The third weight
loss, Td3 (418−438 °C), was related to the graphitization of the
remaining organic structures, leaving a very small carbonaceous
residue at temperatures above 450 °C.
For all the prepared PEUAs, the onset of degradation was
more than 50 °C above the melting point of the corresponding
Table 3. Thermal Degradation of Some Selected PEUAs Determined by TGA
a
a
a
PEUA
chain extender
Td1 (°C)
% weight loss
Td2 (°C)
% weight loss
Td3 (°C)
b
c
PU-1H-18
PU-2H-26
PU-3H-44
PU-3H-64
PU-3H-73
PU-3B-72
PU-3E-71
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
BDA-2CL
EDA-2CL
269
265
257
268
264
272
277
85 (82)
289
315
303
306
302
297
297
9 (12)
436
432
434
432
424
418
428
b
c
75 (74)
15 (17)
b
c
65 (56)
23 (29)
b
c
38 (36)
38 (43)
b
c
30 (27)
47 (49)
b
c
36 (28)
34 (47)
b
c
64 (29)
17 (45)
a
b
c
Calculated from the value of the maximum in the derivative of weight. Calculated from weight feed of PCL. Calculated from weight feed of
diamide−diol chain extender.
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Table 4. Thermal Properties of the Synthesized Poly(ester−urethane−amide)s (PEUAs)
a
a
a
b
a
a
c
PEUA
chain extender
HS (wt %)
Tg (°C)
Tm1 (°C)
ΔH1 (J/g)
xi(PCL) (%)
Tm2 (°C)
ΔH2 (J/g)
ΔH2 (J/gHS)
PU-1E-17
PU-1E-31
PU-1E-41
PU-2E-24
PU-2E-41
PU-2E-52
PU-3E-43
PU-3E-62
PU-3E-71
PU-1B-18
PU-1B-32
PU-1B-42
PU-2B-25
PU-2B-42
PU-2B-53
PU-3B-43
PU-3B-63
PU-3B-72
PU-1H-18
PU-1H-33
PU-1H-43
PU-2H-26
PU-2H-43
PU-2H-54
PU-3H-44
PU-3H-64
PU-3H-73
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
EDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
BDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
HDA-2CL
17
31
41
24
41
52
43
62
71
18
32
42
25
42
53
43
63
72
18
33
43
26
43
54
44
64
73
−53
−53
−54
−53
−52
−54
−35
−29
−16
−53
−54
−55
−53
−53
−53
−40
−31
−18
−53
−54
−55
−53
−54
−53
−40
−34
−30
40
28
22
20
15
12
25.4
17.6
13.9
13.4
7.1
22.6
18.8
17.4
13.0
8.9
88
160
176
134
161
168
136
167
179
89
4.1
19.0
23.2
12.6
24.9
30.0
19.3
38.1
33.0
6.0
24.1
61.3
56.6
52.5
60.7
57.7
44.9
61.4
46.5
33.3
61.9
63.6
46.4
56.4
64.5
52.6
60.8
50.0
13.9
43.6
74.2
48.5
47.0
76.3
44.5
53.1
57.5
3.9
6.0
40
31
29
26
16
13
26.4
17.9
13.6
16.4
6.7
23.8
19.4
17.3
16.2
8.5
153
162
124
147
167
128
150
152
92
19.8
26.7
11.6
23.7
34.2
22.6
38.3
36.0
2.5
3.7
5.8
38
25
22
22
9
23.8
13.4
11.1
15.1
4.1
21.4
14.5
14.4
15.1
5.3
122
154
125
124
157
109
130
138
14.4
31.9
12.6
20.2
41.2
19.6
34.0
42.0
7
3.0
4.8
HDA-2CL
a
b
c
Determined by DSC. Calculated from ΔH1. Calculated from ΔH2
higher, as expected, with a decrease on the SS crystallinity when
HS content increased due to the increase on the rigidity of the
material (see Figure 7). Even for the PEUAs with the lowest
HS content, SS crystallinity was well below 65% and the
melting point below 48−52 °C, the values reached for PCL
Figure 6. DSC thermograms (second scan) of PEUAs derived from
EDA-2CL with molar ratio 1:1.5:0.5 and different PCL diol length.
values are much higher than for polymers PU-3E-62, PU-3B-63,
and PU-3H-64 (−29 to −34 °C). This demonstrates that phase
separation was enhanced in the PEUAs synthesized in this
work, providing a much better defined phase-separated
morphology.
Melting point of the crystallized SS was always higher for
PEUAs with PCL of 1923 g/mol than for PEUAs based on
PCL of 1243 g/mol. In general, also the SS crystallinity was
Figure 7. Effect of HS content on the crystallinity of PCL for PEUAs
based on PCL of 1923 g/mol (open symbols) and 1243 g/mol (filled
symbols) and EDA-2CL (circles), BDA-2CL (squares), and HDA-2CL
(triangles).
I
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homopolymers of different length.34 It is the consequence of
the mobility restrictions at the PCL chain ends. From the graph
it seems that SS crystallinity for PEUAs based on EDA-2CL
and BDA-2CL reaches similar values at the same HS content,
whereas PEUAs based on HDA-2CL tend to have slightly lower
SS crystallinity.
Figure 6, top curve). In addition, the HS melting peak was
broad, and sometimes it slightly merged with the SS melting
peak. These facts made difficult to calculate precisely the area of
the peak. Nevertheless, some trends could be identified.
For PEUAs with the same chemical structure (the same PCL
length and the same chain extender) HS melting point tended
to increase with the increase in HS content (increase in molar
ratio), for example PU-2B-25 < PU-2B-42 < PU-2B-53
(continuous line in Figure 8). This is due to the increase in
the length of the hard segments. When the data were related to
the chemical structure of the PEUAs, other trends were found.
Thus, for PEUAs with the same HS content and the same PCL
length, HS melting point decreased when the length of the
chain extender increased, for example PU-1E-31 > PU-1B-32 >
PU-1H-33 (dotted line in Figure 8). It is the same trend found
for the HS models, and it is due to the lower concentration of
hydrogen bonds when the length of the chain extender
increases. And for PEUAs with the same HS content and the
same chain extender (the series with ∼41% HS content), HS
melting point decreased when the length of the PCL decreased,
for example, PU-1E-41 > PU-2E-41 > PU-3E-43 (broken line in
Figure 8). This tendency was expected because the length of
the hard segment should increase according to the
stoichiometry.
In Figures 8 and 9, the values for HS melting point and HS
melting enthalpy (corrected for the HS content in the
Compared to the HS models, the maximum melting point
reached in the synthesized PEUAs was always below the
melting point of the HS models (see Table 1, run 1). This is
related to the lower length of the HS in the PEUAs respect to
the HS models, although the difference decreased when the
length of the chain extender increased (for HDA-2CL chain
extender the difference is lower).
Figure 8. Effect of HS content on the HS melting point for the
synthesized PEUAs. Symbols as in Figure 7 and for the PEUAs based
on PCL of 539 g/mol: EDA-2CL (plus sign), BDA-2CL (diamond),
and HDA-2CL (right-pointing triangle).
The analysis of the HS melting enthalpy (Figure 9) allowed
for the clear differentiation between the PEUAs with HS
content below 20%, with enthalpy values below 33 J/gHS and
PEUAs with HS content above 20%, with high enthalpy values
in between 44 and 76 J/gHS. The PEUAs with less than 20%
hard segment and the PEUAs with the lowest HS melting point
have the shortest length of the HS, and it is not enough for a
good crystallization of the HS. No trend was found in the data
respect to any of the variables. For PEUAs based on EDA-2CL
and BDA-2CL chain extenders, the maximum enthalpy reached
for any polymer was below the melting enthalpy of the HS
model (see Table 1), calculated either in the first run or in the
second run. Nevertheless, the values were not far from the
melting enthalpy of the HS model on the second run for the
polymers with the highest values of enthalpy. Surprisingly, the
PEUAs based on HDA-2CL chain extender also exhibited high
values of HS melting enthalpy, in contrast with the very low
value found in the second run for the corresponding HS model.
We have not explanation for this behavior. If the reason was the
lower mobility of the long chains in the HS model for
recrystallization from the melt respect to the shorter HS chains
in the PEUAs, the same should hold for EDA-2CL- and BDA-
2CL-based HS models, but these two models were able to
recrystallize from the melt in a very high extent.
Figure 9. Effect of HS content on the HS melting enthalpy for the
synthesized PEUAs. Symbols as in Figure 8.
Small-Angle X-ray Scattering (SAXS). A broad single peak
was observed in SAXS, as usually found in multiblock
copolymers such as these PEUAs. When the samples were
heated, the same behavior was always found, and the peak
disappeared when the HS melted, leaving a homogeneous melt.
On cooling, a broad single peak appeared again, demonstrating
the reversibility of the phase-separated structure. The curves for
polymers) are represented. For both sets of data, the scattering
was very pronounced because it was difficult to properly
analyze the endotherm peak assigned to HS melting. It usually
presented several peaks (see Figure 6), and the listed value was
calculated from the peak maximum, but sometimes it did not
correspond with the peak at the highest temperature (see
J
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PU-2H-43 are given in Figure S1 of the Supporting
Information.
Two parameters were calculated over the scattering curve: (i)
the relative invariant, Q′, as the integral below the curve Iq2 vs q
in between the detector limits, which is related to the extent of
the phase separation, and (ii) the maximum on the scattering
curve, qmax, related to the size scale of the separated phases,
calculated also from the curve Iq2 vs q. It is well-known that for
lamellar systems the length scale (L) of the phase separation
can be calculated directly from the curve Iq2 vs q, while for
other morphologies a calculation of L from the I vs q curve
gives more realistic results. For the current copolymers, we do
not know if a lamellar morphology is present, but we are more
interested on the changes with temperature than on the
absolute values, and the representation Iq2 vs q highlights the
maximum and makes it easier to detect, especially when using
automated macros for the processing of the high amount of
data generated in a synchrotron experiment. Therefore, this will
be the criterion used here to get information on L.
In Figure 10, the changes in Q′ and qmax during the heating
cycle are represented for polymer PU-2E-52. Initially, Q′
Figure 11. Effect of HS content on the size scale (L) of the phase-
separated morphology in the PEUAs based on PCL of 1923 g/mol
(open circles), 1243 g/mol (filled squares), and 539 g/mol (open
triangles).
morphology for the phases below 54% to a dispersed soft
segment phase in a continuous HS matrix above 54%. No other
trends were evident from the data, except for the linear increase
on L with HS content for PEUAs based on the longer PCL diol
(circles in Figure 11) in the HS interval studied here (17−
43%).
Mechanical Properties. The mechanical properties of the
prepared PEUAs are listed in Table 5. Polymers that formed a
gel during reaction, PU-3E-43, PU-3E-71, and PU-3B-72, and
polymer PU-3H-73, were too fragile, and their properties could
not be measured. All polymers behaved as tough materials with
a fast increase in stress at low strains followed, depending on
the polymer, by a slower increase in stress when strain increases
until failure (Figure S2 in the Supporting Information).
Polymers with the lowest HS content, PU-1E-17, PU-1B-18,
and PU-1H-18, presented a significant amount of crystallized
SS, and a clear yield point could be detected on the stress−
strain curve.
Figure 10. Changes in the relative invariant, Q′ (circles), and the
maximum of the scattering curve, qmax (squares), during the heating
cycle for PEUA PU-2E-52.
In Figure 12, the results for stress at break, strain at break,
and modulus are represented. The modulus increased and the
strain at break decreased when the HS content on the polymer
increased. The exception for these trends was the three
polymers with the lowest HS content. These polymers showed
a slightly higher value for the modulus and smaller values for
strain at break than expected due to the crystalline PCL present
in these polymers. The trend for the rest of the polymers was as
expected for materials that increase their rigidity when the HS
content on the material increases. The values of stress at break
increased steadily with the HS content for contents above 30%,
but for lower HS contents, measured values were scattered. The
stress at break values span from 8 to 24 MPa, thus it can be said
that these polymers have good mechanical properties.
No other noticeable trend related to the length of the PCL
diol or to the structure of the chain extender was found in the
data. It can be concluded that HS content is the main
slightly increased with temperature due to a thermal effect, and
when HS started to melt, Q′ decreased until complete melting.
For some of the prepared PEUAs, with high soft segment
content and partially crystallized PCL, a small drop in Q′ was
seen when the PCL melted. The melting range for HS was
quite wide, as already observed by DSC. In the other hand, qmax
did not vary much until complete melting approached and the
SAXS peak disappeared.
The long spacing (L) for the prepared PEUAs was measured
at 50 °C and listed in Table S3 of the Supporting Information
and represented in Figure 11. In general terms, it can be seen
that L value lies in between 11 and 13 nm up to a HS content
of 54%. From this value, L decreases when HS content
increases. This change in the trend could be related to a change
in the material morphology, from probably cocontinuous
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Table 5. Mechanical Properties of the Poly(ester−urethane−amide)s (PEUA)s
PEUA
stress at yield (MPa)
5.2 0.2
strain at yield (%)
stress at break (MPa)
strain at break (%)
modulus (MPa)
PU-1E-17
PU-1E-31
PU-1E-41
PU-2E-24
PU-2E-41
PU-2E-52
PU-3E-43
PU-3E-62
PU-3E-71
PU-1B-18
PU-1B-32
PU-1B-42
PU-2B-25
PU-2B-42
PU-2B-53
PU-3B-43
PU-3B-63
PU-3B-72
35
26
46
4
4
5
12.3 1.0
10.4 1.3
10.6 0.9
1010 190
370 180
190 60
37
45
3
3
5
4
6
6
69
24
4
1500 200
77 17
36
10.0 0.4
11.4 0.3
94
37
9
129
a
a
17
4
80 30
210 30
6.1 0.2
9.7 0.5
10.0 0.3
10.7 0.3
10.5 0.2
9.9 0.4
13.3 0.4
9.7 0.7
15.3 0.6
560 90
220 30
100 20
680 70
60 10
65
73
4
2
5
2
2
127
30
89
80 30
148 10
200 70
81
4
9
34
5
165
a
PU-1H-18
PU-1H-33
PU-1H-43
PU-2H-26
PU-2H-43
PU-2H-54
PU-3H-44
PU-3H-64
PU-3H-73
4.8 0.2
11.4 0.7
8.4 0.2
880 80
174 16
110 40
1080 70
37
66
2
3
6
2
5
12
4
120
20
18.3 1.2
10.2 0.7
15.2 0.8
13.5 0.6
40
4
104
58 15
230 20
90
210 30
410 40
7
15
3
20
7
b
a
b
Gel was formed during reaction and properties could not be measured. The material was too fragile and properties could not be measured.
parameter that governs the mechanical properties of these
PEUAs.
maximum 3.4 wt % after immersion in phosphate buffer
solution at 37 °C for 7 months.35 In this work, it was
demonstrated that degradation took place preferentially
through ester bond cleavage.
For PEUAs derived from PCL with 1243 g/mol molecular
weight, e.g. PU-2E-52, PU-2B-25, and PU-2B-42, the initial loss
at short times was slightly higher than for the polymers based
on PCL with 1923 g/mol molecular weight. This was probably
because of the shorter length of the hard segments (due to the
stoichiometry) which lead to a higher fraction of low molecular
weight species. After the initial step, the rate of degradation was
similar, for these samples, with all the curves running practically
parallel.
A different behavior was found for PEUAs based on PCL
with 539 g/mol molecular weight. Swelling of these samples
was clearly observed as an increase in weight at short times,
followed by weight decay due to the extraction of low
molecular weight species (see PU-3B-43 in Figure 13). When
the polymer was cross-linked, e.g. PU-3E-72 in Figure 13, the
decay at short times did not take place. In that sample
maximum swelling was reached at longer times followed by the
slow decay produced by the hydrolytic degradation. This
difference in swelling behavior for samples based on the
shortest PCL respect to samples based in longer PCL diols was
already found in polymers with HS based on amino acids.13 For
those polymers, the HS was mixed with the PCL soft segments,
increasing the hydrophilicity of the material. As a consequence,
the level of swelling was much higher than for the materials
described in this work, for which the hard segment is phase-
separated and crystalline. Although the swelling of polymers
based on PCL of 539 g/mol allows for the exposure of more
Water Uptake and Degradation. Some samples of PEUAs
were immersed in a phosphate buffer solution at 37 °C, and
their weight change was monitored at certain time intervals. In
Figure 13 weight change (%) vs time (h) is plotted for eight
different PEUAs with different PCL chain length and hard
segment type.
In general, all PEUAs derived from PCL with 1923 g/mol
molecular weight, e.g., PU-1B-18, PU-1B-32, and PU-1B-42,
showed a negligible water absorption and swelling. The small
initial loss at short times is probably due to the release of
oligomers, as found for polymers with hard segments based in
amino acids13 and aliphatic segmented poly(ester−amide)s
based on poly(butylene adipate) and EDA + 2CL or BDA +
2CL.35 The increase in HS content could increase the
hydrophilic environment in the PEUA inducing polymer
swelling. However, this fact was not observed because the
crystallinity of the HS acted as a barrier to water penetration.
The rate of degradation after the initial loss was very slow, and
almost not weight change was produced after 2 months, the
longest time of measurements for these materials. Similar
results were obtained for aliphatic poly(ester−urethane)s based
on poly(butylene adipate) of 2000 g/mol molecular weight.36
These polyurethanes showed essentially no degradation after
immersion in seawater for 160 days. It is known that PCL, used
in our PEUAs, hydrolyzes more slowly than poly(butylene
adipate), and therefore, slower degradation rates are expected
for our PEUAs compared to the polyurethanes in this reference.
Also, poly(ester−amide)s based on poly(butylene adipate) and
EDA + 2CL or BDA + 2CL showed minimal weight losses of
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Figure 13. Weight change with time of immersion in phosphate buffer
solution at 37 °C for hydrated PEUAs.
CL were prepared in high purity and used in the synthesis of
model poly(urethane−amide)s hard segments and new
segmented poly(ester−urethane−amide)s (PEUAs).
Hard segments (HS) derived from these DCE and 1,6-
diisocyanatohexane (HDI) or 1,4-diisocyanatobutane were
highly crystalline with high melting points. HS derived from
L-lysine diisocyanate showed lower melting points with a much
lower crystallinity.
PEUAs derived from PCL diols of molecular weight 539,
1243, or 1923 g/mol, HDI, and these three DCE presented a
phase-separated morphology as proved by DSC and SAXS,
even at a HS content as low as 17%.
HS melting point in the PEUAs was lower than for the
corresponding HS models due to the shorter length of the
segments and increased when HS content increased. For
PEUAs of the same HS content and the same PCL length, HS
melting point decreased when the length of DCE increased due
to the lower concentration of hydrogen bonds. For PEUAs of
the same HS content and the same DCE, HS melting point
decreased when the length of the PCL decreased because the
length of the HS increased.
Thermal degradation of these PEUAs was well above the
melting point of the HS, allowing for the melt processing of
these materials. HS was thermally less stable than PCL soft
segment, with a slight dependence on chain extender length.
SAXS analysis demonstrated that at temperatures above the
melting of the HS the PEUAs became a homogeneous material
that separated again in phases on cooling. The length scale of
the phase-separated structure was fairly constant and decreased
when HS content was above 54%, probably due to a change in
morphology.
Mechanical properties were good and were mainly affected
by the HS content.
Water uptake was negligible for PEUAs with the longer PCL
diols and very small for PEUAs with the shortest PCL diol due
to the crystallinity of the hard segment. Degradation rate was
very slow, and the degradation mechanism was proven to be by
surface erosion.
Figure 12. Mechanical properties of the synthesized PEUAs. From top
to bottom: stress at break, strain at break, and modulus. Symbols as in
Figure 11.
material to hydrolysis, the rate of degradation was still very
slow, similar to the polymers based on longer PCL diols.
Some PEUA samples were analyzed by SEM after 2 months
degradation in phosphate buffer at 37 °C. In Figure 14, three
different films derived from PU-2B-42, PU-3B-43, and PU-2H-
43 are shown. Slight erosion on the surface of the film was
appreciated in these PEUA samples. Similar eroded surfaces
were seen for the rest of degraded PEUAs. The same superficial
erosion pattern has been reported for other polyester-based
segmented polymers.13,35
The PEUAs described in this work are materials of good
processability and good mechanical properties with a potential
use as biodegradable materials for applications requiring long
degradation times.
CONCLUSIONS
Three diamide−diol chain extenders (DCE) derived from
linear aliphatic diamines of different length (n = 2, 4, 6) and ε-
■
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Figure 14. SEM micrographs for PEUAs films surfaces degraded by hydrolysis in a phosphate buffer solution at 37 °C after 2 months: (a, b) PU-2B-
25; (c, d) PU-3B-43; (e, f) PU-2H-43.
(8) Siparsky, G. L.; Voorhees, K. J.; Miao, F. J. Environ. Polym.
Degrad. 1998, 6, 31−41.
(9) Li, S. M.; Chen, X. H.; Groos, R. A.; McCarthy, S. P. J. Mater. Sci.:
ASSOCIATED CONTENT
■
S
* Supporting Information
Series of the synthesized poly(ester−urethane−amide)s;
solubility and long spacing of the polymers; real time SAXS
curves and stress−strain curves. This material is available free of
charge via the Internet at http://pubs.acs.org.
Mater. Med. 2000, 11, 227−233.
(10) Bogdanov, B.; Toncheva, V.; Schacht, E.; Finelli, L.; Sarti, B.;
Scandola, M. Polymer 1999, 40, 3171−3182.
(11) Gorna, K.; Gogolewski, S. Polym. Degrad. Stab. 2002, 75, 113−
122.
(12) Bae
Richa, A. Polymer 2006, 47, 8420−8429.
(13) Marcos-Fernandez, A.; Abraham, G. A.; Valentín, J. L.; San
Roman
́ ́ ́
z, J. E.; Marcos-Fernandez, A.; Lebron-Aguilar, R.; Martínez-
AUTHOR INFORMATION
■
Corresponding Author
*E-mail amarcos@ictp.csic.es; Tel (+34) 912 587 555; Fax
(+34) 915 644 853.
́
́
, J. Polymer 2006, 47, 785−798.
(14) Ding, M.; Li, J.; Fu, X.; Zhou, J.; Tan, H.; Gu, Q.; Fu, Q.
Biomacromolecules 2009, 10, 2857−2865.
Notes
́ ́
(15) Abraham, G. A.; Marcos-Fernandez, A.; San Roman, J. J. Biomed.
The authors declare no competing financial interest.
Mater. Res. 2006, 76A, 729−736.
(16) Hassan, M. K.; Mauritz, K. A.; Storey, R. F.; Wiggins, J. S. J.
Polym. Sci., Polym. Chem. 2006, 44, 2990−3000.
ACKNOWLEDGMENTS
■
We are indebted to the Ministry of Science and Innovation
(MICINN) in Spain for their economic support of the work
(MAT2008-00619 and MAT 2011-25513) and the access to
the synchrotron radiation source (experiments 16-2-87 and 16-
2-94) in the European Synchrotron Radiation Facility (ESRF)
in Grenoble, France. We are grateful to Dr. Ana Labrador and
(17) Tatai, L.; Moore, T. G.; Adhikari, R.; Malherbe, F.; Jayasekara,
R.; Griffiths, I.; Gunatillake, P. A. Biomaterials 2007, 28, 5407−5417.
́
́ ́
dez-dArlas, B.; Rueda, L.; de la Caba, K.; Mondragon, I.;
(18) Fernan
Eceiza, A. Polym. Eng. Sci. 2008, 48, 519−529.
(19) Heijkants, R. G. J. C. Polyurethane scaffolds as meniscus
reconstruction materials. Ph.D. Thesis, University of Groningen, The
Netherlands, 2004.
Dr. Franco
J.L.V. thanks Secretaria de Estado de Investigacion
Innovacion (Spain) for his Ramon y Cajal contract. J.E.B. is
much indebted to Consejo Nacional de Ciencia y Tecnologia
(CONACYT, Mexico) for a postdoctoral fellowship (Exp.
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